A comparison was made between the predicted 96-h guppy LC50s of 110 phenols based upon QSAR equations of Saarikoski and Viluksela and the data from 936 toxicity screening tests for these chemicals. Test data on up to eight species of freshwater fishes were available per compound. Overall, the experimental toxicity data on these chemicals were consistent with the QSAR predictions. The 110 phenols occupy a considerably larger range of spanned substituent space than the QSAR training set. One compound, 4-aminophenol (14), exhibited lethality at test concentrations of 35 times below that predicted. The increased fish toxicity of this compound is explained in terms of a proelectrophile molecular mechanism, in which the parent compound is metabolically oxidized to a para quinoid structure. The resulting electrophilic metabolite is susceptible to attack by nucleophilic moieties present in biological macromolecules leading to covalent bond formation and inhibition of biochemical processes.